Breast cancer is the most common type of cancer among women in Western nations, affecting more than 180,000 women in the U.S. each year. The disease arises in the mammary gland, which is made up of a branching duct system. Each mammary gland, or breast, contains 15 to 20 sections called lobes, and each lobe contains a series of branched ducts that drain into the nipple. Epithelial cells that line each duct are responsible for milk production. Invasive breast cancer is thought to originate from normal epithelium of the terminal duct/lobular unit through a series of increasingly abnormal proliferative lesions. Once the tumor acquires the ability to metastasize, breast cancer cells spread to other organs, making treatment increasingly more difficult. The most common sites of breast cancer metastases are the lung, liver, and bones. Metastases to the bone are commonly associated with severe pain, loss of bone, and increased risk of fractures. Many anti-estrogenic therapies used in the treatment of breast cancer are also associated with accelerated bone loss.
Patients diagnosed with breast cancer typically undergo surgery and/or radiotherapy to treat the primary tumor, followed by adjuvant therapy to treat any cancer cells that may have spread to distant sites. Adjuvant therapy consists of cytotoxic chemotherapy and/or endocrine therapy. Although chemotherapy has been effective in treating various types of malignancies, many anti-neoplastic compounds induce undesirable side effects. Additionally, many tumors either fail to respond or become resistant to chemotherapy and endocrine therapies. While adjuvant therapy has improved the mortality rate among breast cancer patients, the 10-year survival rate for patients with the most common histopathological types of invasive breast cancer is still only 35-50% (Weigelt et al. 2005 Nat. Rev. Cancer 5: 591-602). Further, due to poor prognosis criteria, many women that would be cured by local treatment alone receive adjuvant therapy unnecessarily.
Consequently, more efficient and effective molecular targets against breast cancer are needed. Alternative therapies that are less toxic and/or more effective than chemotherapy and endocrine therapies would improve treatment regimens and increase survival. Further, agents that can be used as preventative treatments for patients that may be at risk for developing invasive or metastatic breast cancer would be useful in the clinic. It is an object of the present disclosure, therefore, to provide alternative compositions and methods for treating breast cancer or inhibiting or preventing the progression of breast cancer in patients.